Delphinidin, a dietary anthocyanidin in pigmented fruits and vegetables: a new weapon to blunt prostate cancer growth.
In a recent publication, we have shown that delphinidin, an anthocyanidin induces apoptosis and cell cycle arrest in highly metastatic human prostate cancer (PCa) PC3 cells. Extending these studies, we provide additional evidence that delphinidin induces apoptosis and cell cycle arrest in androgen refractory human PCa 22Rnu1 cells and that these effects are concomitant with inhibition of NFkappaB. We observed that delphinidin treatment to 22Rnu1 cells resulted in a dose-dependent (i) G(2)/M phase cell cycle arrest, (ii) induction of apoptosis (iii) and inhibition of NFkappaB signaling. The induction of apoptosis by delphinidin was mediated via activation of caspases since a general caspase inhibitor Z-VAD-FMK significantly reversed this effect. Delphinidin treatment to cells resulted in a dose-dependent decrease in (i) phosphorylation of IKKgamma (NEMO), (ii) phosphorylation of NFkappaB inhibitory protein IkappaBalpha, (iii) phosphorylation of NFkappaB/p65 at Ser(536) and NFkappaB/p50 at Ser529, (iv) NFkappaB/p65 nuclear translocation, and (v) NFkappaB DNA binding activity. Taken together, our data show that delphinidin induces apoptosis of both androgen independent and androgen refractory human PCa cells via activation of caspases and in addition, this effect might be due to inhibition of NFkappaB signaling. We suggest that delphinidin could be developed as a novel agent against PCa.
Bin Hafeez
Bilal
B
Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53706, USA.
Asim
Mohammad
M
Siddiqui
Imtiaz Ahmad
IA
Adhami
Vaqar Mustafa
VM
Murtaza
Imtiyaz
I
Mukhtar
Hasan
H
D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004032:Diet; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D005638:Fruit / Q000737:chemistry*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010860:Pigments, Biological / Q000737:chemistry*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D015533:Transcriptional Activation / Q000187:drug effects; D014675:Vegetables / Q000737:chemistry*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000872:Anthocyanins; D018797:Cell Cycle Proteins; D016328:NF-kappa B; D010860:Pigments, Biological; D051028:bcl-2-Associated X Protein; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; C017185:delphinidin